Previous studies have revealed several genes involved in the carcinogenesis of oral cancer. However, the detailed mechanisms underlying this process are poorly understood. Previously, we established a database cataloging the transcriptional progression profile of oral carcinogenesis and identified several candidate genes with continuously increasing or decreasing expression, which specifically promote the transition of oral premalignant lesions to invasive carcinomas. In this study, using our microarray database, we attempted to determine significant genes that may contribute to metabolic alterations during oral carcinogenesis. After performing a literature survey, we focused on 15 candidate genes associated with glucose metabolism changes, particularly the tri-carboxylic acid cycle, and investigated the mRNA-expression status of these genes with our database. Only the solute carrier family 2 member 1 gene (also known as GLUT1), showed significantly increased mRNA expression during oral tumorigenesis. Immunohistochemical analysis confirmed that GLUT1 protein expression significantly increased during oral carcinogenesis. In addition, tumors with high expression of this protein significantly correlated with nodal status (P=0.002). Kaplan-Meier survival curves clearly demonstrated the adverse impact of high GLUT1 protein expression on disease-free survival (P=0.004). GLUT1 mRNA and protein expression increased in the order of normal mucosal tissues, epithelial dysplastic lesions and invasive carcinomas. Therefore, metabolic alterations, especially in glucose metabolism, occurred at the very early stage of development of oral malignancies. In addition, GLUT1 played a significant role in oral cancer, acquiring a malignant phenotype.

BackgroundAlthough multilineage cells derived from oral tissue, especially the dental pulp, apical papilla, periodontal ligament, and oral mucosa, have neural crest-derived stem cell (NCSC)-like properties, the differences in the characteristics of these progenitor cell compartments remain unknown. The primary aim of the current study was to elucidate these differences. MethodsMultilineage sphere-forming apical papilla-derived cells (APDCs), periodontal ligament-derived cells (PDLDCs), and oral mucosa stroma-derived cells (OMSDCs) from the same individuals were isolated from impacted developing teeth. All sphere-forming cells were characterized by biological analyses of stem cells. Additionally, composites of these cells and multiporous hydroxyapatite scaffolds were transplanted into immunocompromised mice. ResultsAll sphere-forming cells expressed neural crest-related markers. Although APDCs and PDLDCs showed greater mineralized-cell differentiation, they exhibited poorer differentiation into adipocytes in vitro than OMSDCs. In immunocompromised mice, APDCs were better able to form hard tissues than PDLDCs and OMSDCs. Moreover, the expression of certain tissue-speci c markers, such as CD24 and CD56 (NCAM1), differed among the tissue-derived cells. Surprisingly, the expression of only CD24 and CD56 could be discriminated among human tissues. ConclusionsOur results suggest that although cells having NCSC-like properties present the same phenotype, they differ in the expression of certain markers and differentiation abilities. The present study is the rst to demonstrate the differences in differentiation ability and molecular markers among multilineage human APDCs, PDLDCs, and OMSDCs obtained from the same patients and, concomitantly, the same sites and identify these tissuespeci c markers in the human tooth developmental process.

Background Although multilineage cells derived from oral tissue, especially the dental pulp, apical papilla, periodontal ligament, and oral mucosa, have neural crest-derived stem cell (NCSC)-like properties, the differences in the characteristics of these progenitor cell compartments remain unknown. The primary aim of the current study was to elucidate these differences. Methods Multilineage sphere-forming apical papilla-derived cells (APDCs), periodontal ligament-derived cells (PDLDCs), and oral mucosa stroma-derived cells (OMSDCs) from the same individuals were isolated from impacted developing teeth. All sphere-forming cells were characterized by biological analyses of stem cells. Additionally, composites of these cells and multiporous hydroxyapatite scaffolds were transplanted into immunocompromised mice. Results All sphere-forming cells expressed neural crest-related markers. Although APDCs and PDLDCs showed greater mineralized-cell differentiation, they exhibited poorer differentiation into adipocytes in vitro than OMSDCs. In immunocompromised mice, APDCs were better able to form hard tissues than PDLDCs and OMSDCs. Moreover, the expression of certain tissue-specific markers, such as CD24 and CD56 (NCAM1), differed among the tissue-derived cells. Surprisingly, the expression of only CD24 and CD56 could be discriminated among human tissues. Conclusions Our results suggest that although cells having NCSC-like properties present the same phenotype, they differ in the expression of certain markers and differentiation abilities. The present study is the first to demonstrate the differences in differentiation ability and molecular markers among multilineage human APDCs, PDLDCs, and OMSDCs obtained from the same patients and, concomitantly, the same sites and identify these tissue-specific markers in the human tooth developmental process.